Is ECHDC3 p.Arg29Cys (c.85C>T) pathogenic?

ECHDC3 p.Arg29Cys (c.85C>T) is classified Uncertain significance in ECHDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.1236); Very rare (popmax 0.0011%, nfe).

How common is ECHDC3 p.Arg29Cys (c.85C>T) in the general population?

ECHDC3 p.Arg29Cys (c.85C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about ECHDC3 p.Arg29Cys (c.85C>T)?

AlphaMissense predicts likely benign (score 0.1236) — an in-silico prediction, not a clinical call.

ECHDC3 p.Arg29Cys

c.85C>T · rs1471937421 · VCV3086951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1236 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1236	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.06	GERP -3
Regional constraint	o/e 1.14	unconstrained · MANE · 21 kb · p 0.0091 · regional, not allelic
Overall
CADD	15.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 11/999,054 alleles

Filtering AF 0.000591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000432%

Overall 0.00088% 11/1,249,756 alleles · very rare exomes 11/1,098,558 · genomes 0/151,198 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ECHDC3
Protein: p.Arg29Cys
Coding: c.85C>T
MANE Select: NM_024693
dbSNP: rs1471937421
Type: single nucleotide variant
Location: chr10:11742661 (GRCh38)
Gene constraint: LOEUF 1.614 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 1 PDB

Full ECHDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHDC3 p.Arg29His Uncertain significance ★ ⚠ same residue
ECHDC3 p.Ala173Thr Uncertain significance ★ ⚠ same type
ECHDC3 p.Ala36Gly Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg118His Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg51Gly Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg51Trp Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg8Gln Uncertain significance ★ ⚠ same type
ECHDC3 p.Asn89Asp Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/echdc3-p-arg29cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown